Discovery of a follistatin-derived myostatin inhibitory peptide
Discovery of a follistatin-derived myostatin inhibitory peptide
复制标题
卵泡抑素衍生的肌肉生长抑制素抑制肽的发现
DOI：
10.1016/j.bmcl.2019.126892
复制
发表时间：
2020
影响因子：
2.7
通讯作者：
Hayashi Yoshio
中科院分区：
文献类型：
--
作者：
Saitoh Mariko;Takayama Kentaro;Hitachi Keisuke;Taguchi Akihiro;Taniguchi Atsuhiko;Tsuchida Kunihiro;Hayashi Yoshio
卵泡抑素是众所周知的转化生长因子-β超家族配体的抑制剂，包括肌肉生长抑制素和激活素A。肌肉生长抑制素是肌肉生长的负调控因子，是治疗肌肉萎缩性疾病的有前景的靶点。在这里，我们专注于卵泡抑素(Fst)的当时末端结构域(ND)，它与肌肉生长抑素的I型受体结合部位相互作用。通过对合成的ND衍生片段多肽的生物活性测定，我们鉴定了一种新的肌肉生长抑制素抑制14肽，它能有效地抑制肌肉生长抑素，但不能抑制激活素A或转化生长因子-β1。肌肉注射，DF-3显著增加小鼠的骨骼肌质量，因此，它可以作为一个基于肌肉抑制素抑制的肌肉增强发展的平台。
Follistatin is well known as an inhibitor of transforming growth factor (TGF)-β superfamily ligands including myostatin and activin A. Myostatin, a negative regulator of muscle growth, is a promising target with which to treat muscle atrophic diseases. Here, we focused on theN-terminal domain (ND) of follistatin (Fst) that interacts with the type I receptor binding site of myostatin. Through bioassay of synthetic ND-derived fragment peptides, we identified DF-3, a new myostatin inhibitory 14-mer peptide which effectively inhibits myostatin, but fails to inhibit activin A or TGF-β1, in anin vitroluciferase reporter assay. Injected intramuscularly, DF-3 significantly increases skeletal muscle mass in mice and consequently, it can serve as a platform for development of muscle enhancement based on myostatin inhibition.